Pharmacokinetics-pharmacodynamics of sertraline as an antifungal in HIV-infected Ugandans with cryptococcal meningitis

AbstractThe ASTRO-CM dose-finding pilot study investigated the role of adjunctive sertraline for the treatment of HIV-associated cryptococcal meningitis in HIV-infected Ugandan patients. The present study is a post hoc pharmacokinetic-pharmacodynamic analysis of the ASTRO-CM pilot study to provide insight into sertraline exposure –response–outcome relationships. We performed a population pharmacokinetic analysis using sertraline plasma concentration data and correlated various predicted PK-PD indices with the percentage change in log10 CFU/mL from baseline. Sertraline clearance was 1.95-fold higher in patients receiving antiretroviral (ART), resulting in 49% lower drug exposure. To quantify the clinical benefit of sertraline, we estimated rates of fungal clearance from cerebrospinal fluid (CSF) of ASTRO-CM patients using Poisson model and compared the clearance rates to a historical control study (COAT) in which patients received standardCryptococcus therapy of amphotericin B (0.7 –1.0 mg/kg per day) and fluconazole (800 mg/day) without sertraline. Adjunctive sertraline significantly increased CSF fungal clearance rate compared to COAT trial and sertraline effect was dose-independent with no covariate found to affect fungal clearance including ART. Study findings suggest sertraline response could be mediated by different mechanisms than directly inhibiting the initiation of protein translation as previously suggested; this is supported by the predi...
Source: Journal of Pharmacokinetics and Pharmacodynamics - Category: Drugs & Pharmacology Source Type: research

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Publication date: Available online 11 December 2019Source: Medicina Intensiva (English Edition)Author(s): F.G. Márquez-Villegas, A. Elizalde-Figueroa, J.P. Venzor-Castellanos
Source: Medicina Intensiva - Category: Intensive Care Source Type: research
CONCLUSIONS: A complete recovery of cranial nerves VII and VIII in the course of RHS can be achieved. PMID: 31816219 [PubMed - as supplied by publisher]
Source: Neuroendocrinology Letters - Category: Endocrinology Tags: Neuro Endocrinol Lett Source Type: research
AbstractA regional epidemic of aseptic meningitis caused by echovirus 30 (E30) occurred in Hokkaido, Japan, during the period of August-December 2017. To investigate their phylogenetic relationship to other human enteroviruses, we determined the complete genomic nucleotide sequences of isolates from this outbreak. Phylogenetic analysis of the viral capsid protein 1 gene showed that the strains were most closely related to E30 strains detected in Germany, France, and Russia in 2013. In contrast, the region encoding the viral protease and the RNA-dependent RNA polymerase had a close phylogenetic relationship to non-E30 enter...
Source: Archives of Virology - Category: Virology Source Type: research
Streptococcus suis is a major swine pathogen causing arthritis, meningitis and sudden death in post-weaning piglets and is also a zoonotic agent. S. suis comprises 35 different serotypes of which the serotype 2 i...
Source: BMC Veterinary Research - Category: Veterinary Research Authors: Tags: Research article Source Type: research
Immune checkpoint inhibitors (ICIs) can cause adverse reactions in the nervous system. The incidence rate is 0.1% –12% and 80% of nervous system adverse reactions occur within the first four months of application. ICIs can cause diseases of various parts of the nervous system including central nervous system diseases such as aseptic meningitis, meningeal encephalitis, necrotizing encephalitis, brainstem encep halitis, transverse myelitis, etc., and peripheral neuropathy such as cranial nerve peripheral neuropathy, multifocal nerve root neuropathy, Guillain‐Barré syndrome, spinal nerve root neuropathy, myasth...
Source: Thoracic Cancer - Category: Cancer & Oncology Authors: Tags: CLINICAL GUIDELINE Source Type: research
Conditions:   Meningitis;   Encephalitis;   Abscess Brain Intervention:   Other: Pragmatic, multi-component package Sponsors:   University of Liverpool;   National Institute for Health Research, United Kingdom;   Christian Medical College, Vellore, India;   National Institute of Mental Health and Neuro Sciences, India;   Oswaldo Cruz Foundation;   Malawi-Liverpool-Wellcome Trust Clinical Research Programme;   University of Malawi College of Medicine;   University of Warw...
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Vessel wall MR imaging may be helpful in diagnosing and monitoring the treatment of vasculitic complications from CNS infections.
Source: Neurology Clinical Practice - Category: Neurology Authors: Tags: Childhood stroke, MRI, Meningitis, Pediatric stroke; see Cerebrovascular Disease/ Childhood stroke Case Source Type: research
Abstract Viruses in species Parechovirus A (Picornaviridae) are associated with a wide variety of clinical manifestations. Parechovirus A3 (PeV-A3) is known to cause sepsis-like illness, meningitis, and encephalitis in infants and young children. To date, no specific therapies are available to treat PeV-A3-infected children. We had previously identified two FDA-cleared antifungal drugs, itraconazole (ITC) and posaconazole (POS) with potent and specific antiviral activity against PeV-A3. Time-of-addition and synchronized infection assays revealed that POS targets an early stage of the PeV-A3 life cycle. POS exerts ...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research
Bacterial meningitis is a severe infection with substantial mortality and morbidity.(1,2) In adults and children after the neonatal period the most common pathogens are Streptococcus pneumoniae and Neisseria meningitis, while in neonates Streptococcus agalactiae (group B streptococci; GBS) causes the majority of cases.(1 –3) In large cohort studies of adults with community acquired bacterial meningitis 0.4-7.4% of all cases were caused by GBS.(4–6) Few studies have specifically addressed GBS meningitis in adults.(7–9) One retrospective cohort study and review of literature published in 1997, stated that m...
Source: Journal of Infection - Category: Infectious Diseases Authors: Source Type: research
A mother whose baby got meningitis because of Group B Strep says all pregnant women should be tested.
Source: BBC News | Health | UK Edition - Category: Consumer Health News Source Type: news
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